Adjoining Segments Research Articles

Controlling retention, selectivity and magnitude of EOF by segmented monolithic columns consisting of octadecyl and naphthyl monolithic segments – applications to RP‐CEC of both neutral and charged solutes

Monolithic capillaries made of two adjoining segments each filled with a different monolith were introduced for the control and manipulation of the electroosmotic flow (EOF), retention and selectivity in reversed phase-capillary electrochromatography (RP-CEC). These columns were called segmented monolithic columns (SMCs) where one segment was filled with a naphthyl methacrylate monolith (NMM) to provide hydrophobic and π-interactions, while the other segment was filled with an octadecyl acrylate monolith (ODM) to provide solely hydrophobic interaction. The ODM segment not only provided hydrophobic interactions but also functioned as the EOF accelerator segment. The average EOF of the SMC increased linearly with increasing the fractional length of the ODM segment. The neutral SMC provided a convenient way for tuning EOF, selectivity and retention in the absence of annoying electrostatic interactions and irreversible solute adsorption. The SMCs allowed the separation of a wide range of neutral solutes including polycyclic aromatic hydrocarbons (PAHs) that are difficult to separate using conventional alkyl-bonded stationary phases. In all cases, the k' of a given solute was a linear function of the fractional length of the ODM or NMM segment in the SMCs, thus facilitating the tailoring of a given SMC to solve a given separation problem. At some ODM fractional length, the fabricated SMC allowed the separation of charged solutes such as peptides and proteins that could not otherwise be achieved on a monolithic column made from NMM as an isotropic stationary phase due to the lower EOF exhibited by this monolith.

Parts-Per-Billion Fourier Transform Ion Cyclotron Resonance Mass Measurement Accuracy with a “Walking” Calibration Equation

Ion cyclotron resonance frequency, f, is conventionally converted to ion mass-to-charge ratio, m/z (mass "calibration") by fitting experimental data spanning the entire detected m/z range to the relation, m/z = A/f + B/f(2), to yield rms mass error as low as ~200 ppb for ~10,000 resolved components of a petroleum crude oil. Analysis of residual error versus m/z and peak abundance reveals that systematic errors limit mass accuracy and thus the confidence in elemental composition assignments. Here, we present a calibration procedure in which the spectrum is divided into dozens of adjoining segments, and a separate calibration is applied to each, thereby eliminating systematic error with respect to m/z. Further, incorporation of a third term in the calibration equation that is proportional to the magnitude of each detected peak minimizes systematic error with respect to ion abundance. Finally, absorption-mode data analysis increases mass measurement accuracy only after minimization of systematic errors. We are able to increase the number of assigned peaks by as much as 25%, while reducing the rms mass error by as much as 3-fold, for significantly improved confidence in elemental composition assignment.

Influence of pre-existing fabrics on fault kinematics and rift geometry of interacting segments: Analogue models based on the Albertine Rift (Uganda), Western Branch-East African Rift System

This study aims at showing how far pre-existing crustal weaknesses left behind by Proterozoic mobile belts, that pass around cratonic Archean shields (Tanzania Craton to the southeast and Congo Craton to the northwest), control the geometry of the Albertine Rift. Focus is laid on the development of the Lake Albert and Lake Edward/George sub-segments and between them the greatly uplifted Rwenzori Mountains, a horst block located within the rift and whose highest peak rises to >5000 m above mean sea level. In particular we study how the southward propagating Lake Albert sub-segment to the north interacts with the northward propagating Lake Edward/George sub-segment south of it, and how this interaction produces the structures and geometry observed in this section of the western branch of the East African Rift, especially within and around the Rwenzori horst. We simulate behaviour of the upper crust by conducting sandbox analogue experiments in which pre-cut rubber strips of varying overstep/overlap connected to a basal sheet and oriented oblique and/or orthogonal to the extension vector, are placed below the sand-pack. The points of connection present velocity discontinuities to localise deformation, while the rubber strips represent ductile domain affected by older mobile belts. From fault geometry of developing rift segments in plan view and section cuts, we study kinematics resulting from a given set of boundary conditions, and results are compared with the natural scenario. Three different basal model-configurations are used to simulate two parallel rifts that propagate towards each other and interact. Wider overstep (model SbR3) produces an oblique transfer zone with deep grabens (max. 7.0 km) in the adjoining segments. Smaller overlap (model SbR4) ends in offset rift segments without oblique transfer faults to join the two, and produces moderately deep grabens (max. 4.6 km). When overlap doubles the overstep (model SbR5), rifts propagate sub-orthogonal to the extension direction and form shallow valleys (max. 2.9 km). Relative ratios of overlap/overstep between rift segments dictate the kind of transition zone that develops and whether or not a block (like the Rwenzoris) is captured and rotates; hence determining the end-member geometry. Rotation direction is controlled by pre-existing fabrics. Fault orientation, fault kinematics, and block rotation (once in play) reinforce each other; and depending on the local kinematics, different parts of a captured block may rotate with variable velocities but in the same general direction. Mechanical strength anisotropy of pre-structured crust only initially centres fault nucleation and propagation parallel to the grain of weakness of the basement, but at later stages of a protracted period of crustal extension, such boundaries are locally defied.

Grafts are Unnecessary for Proximal Bulbar Reconstruction

We compared our experience with the reconstruction of proximal vs distal bulbar stricture to assess the role of excision and primary anastomosis vs graft procedures at each site. We reviewed all urethroplasties done by a single surgeon during a 2-year period. Data analyzed included patient history and demographics, operative details, stricture length and site, and clinical outcome. The proximal bulbar urethra was defined as the segment within 5 cm of the membranous urethra and the distal bulb was defined as the adjoining segment extending to the penoscrotal junction. Cases involving the pendulous or posterior urethra were excluded from study. Of 210 urethroplasties from 2007 to 2009, 112 were done for bulbar strictures, including 72 (64%) for proximal bulbar strictures. All 72 cases were treated with excision and primary anastomosis. Median stricture length was 2 cm (range 1 to 5), although 31 of 72 strictures (43%) were of intermediate length (2.5 to 5 cm). Recurrence developed in 1 case (1.4%). Distal bulbar strictures in 40 of the 112 cases (36%) were treated predominantly with substitution urethroplasty in 36 (90%), and with excision and primary anastomosis in 4 (10%). Median stricture length was 3.75 cm (range 1.5 to 20). We noted intermediate length stricture in 18 of 40 cases (45%) and recurrence in 11 (28%). Of intermediate length strictures recurrence was much rarer after excision and primary anastomosis than after graft procedures (1 of 33 or 3.0% vs 6 of 16 or 38%, p<0.05). Location is critical when selecting an appropriate technique for bulbar urethral reconstruction. Excision and primary anastomosis are superior to grafts in the proximal bulb. Grafts are often unnecessary for reconstructing proximal bulbar strictures 5 cm or less.

1220 GRAFTS ARE UNNECESSARY FOR PROXIMAL BULBAR RECONSTRUCTION

You have accessJournal of UrologyTrauma/Reconstruction: Trauma & Reconstructive Surgery IV1 Apr 20101220 GRAFTS ARE UNNECESSARY FOR PROXIMAL BULBAR RECONSTRUCTION Ryan Terlecki, Matthew Steele, Celeste Valadez, and Allen Morey Ryan TerleckiRyan Terlecki More articles by this author , Matthew SteeleMatthew Steele More articles by this author , Celeste ValadezCeleste Valadez More articles by this author , and Allen MoreyAllen Morey More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.743AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Strictures of the proximal bulbar urethra have been proposed as being uniquely amenable to excision and primary anastomosis (EPA) procedures as opposed to those occurring more distally (J Urol 2007; 177, p37A). We compared our recent experience with reconstruction of proximal versus distal bulbar strictures to assess the relative role of EPA and graft procedures in each area. METHODS We reviewed our database of all urethroplasties performed by a single surgeon at our referral center during a two year period. Data analyzed included patient history and demographics, operative details, stricture length and location, and clinical outcomes. The proximal bulbar urethra was defined as the segment within 5 cm of the membranous urethra; the distal bulb was defined as the adjoining segment extending to the penoscrotal junction. Cases involving the pendulous or posterior urethra were excluded. RESULTS Of the 210 consecutive men having urethral reconstruction at our center from 2007-2009, 112 had bulbar strictures. Proximal bulbar urethral strictures comprised the majority of cases (72/112, 64%) and all 72 were treated via EPA procedures: no patient with a proximal bulbar stricture required a graft procedure. Median stricture length was 2 cm (range 1-4.5 cm) although 31/72 (43%) were of intermediate length (2.5-5 cm); median stretched penile length (SPL) was 15 cm. Prior to referral, treatment had been performed in 51/72 (71%) of patients, with 10/72 (14%) having prior urethroplasty. At a median follow-up of 358 days, recurrence was seen in only 1/72 (1.4%), a patient with a history of multiple prior urethral dilation procedures. Distal bulbar strictures comprised 40/112 (36%) of cases and were treated predominantly with substitution urethroplasty (36/40, 90%), and less commonly via EPA (4/40, 10%). Median stricture length was 2.5 cm and intermediate length strictures were noted in 18/40 (45%). Prior treatment was noted in 26/40 (65%), with 11/40 (28%) having prior urethroplasty. At a median follow-up of 529 days, recurrence was seen in 11/40 (28%). Among intermediate length strictures, recurrence was seen in only 1/30 (3.3%) of those treated with EPA and in 6/19 (32%) managed by graft procedures (p = 0.02). CONCLUSIONS EPA is associated with superior outcomes compared to graft procedures and should be performed whenever possible. Location is of critical importance in selecting the appropriate reconstructive technique for bulbar urethral strictures and the proximal bulb is uniquely amenable to EPA repairs. Our data strongly suggest that grafts are unnecessary for reconstruction of proximal bulbar strictures < 5 cm. Dallas, TX© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e472-e473 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryan Terlecki More articles by this author Matthew Steele More articles by this author Celeste Valadez More articles by this author Allen Morey More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Selective trapping and concentration of nanoparticles and viruses in dual-height nanofluidic channels

Nanofluidic systems offer advantages for chemical analysis, including small sample volumes, size-selective particle trapping, sample concentration and the ability to separate and detect single molecules. Such systems can be fabricated using planar nanochannels, which rely on standard photolithographic techniques. Nanochannel fluid flow can be driven by capillary action, which benefits from simple injection and reasonably high flow rates. We demonstrate an analysis chip fabricated with planar nanochannels that consist of two adjoining segments of different heights. When nano-analytes elute through the channel, they become physically trapped when the channel dimensions shrink below the size of the particles. We demonstrate the capability of these devices to trap and concentrate by using the following: 120-nm polymer beads, 30-nm polymer beads, Herpes simplex virus 1 capsids, and hepatitis B virus capsids. Each species was fluorescently labeled and its resulting fluorescent signal was detected using a cooled CCD camera. We show how the signal-to-noise ratio of trapped analyte intensity varies linearly with analyte concentration. The goal of this work is to eventually perform size-based fractionation of a variety of nanoparticles, including biomolecules such as proteins.

Degenerative changes in the adjacent segments after stabi¬lizing operations on the vertebral column

This analytical review covered 80 scientific publications. Clinical and experimental studies of degenerative changes in adjoining intervertebral disks after spinal fusion were assessed. The part of the following risk factors in the development of diseases in adjoining segments after spinal fusion was revealed and assessed: character of instrumentation (long or short), type of performed stabilization (union), localization of surgical intervention (spinal segment), sagittal imbalance, state of intervertebral disks at the moment of operation, age and sex of patients, state of bone tissue (osteopenia, osteoporosis). Multifactorial etiology of the disease of adjoining segments after spinal fusion was proved.

A basis of multi-degree splines

This paper defines a basis of MD-splines, which are B-spline-like curves comprised of polynomial segments of various degrees (MD stands for “multi-degree”). This basis is nonnegative, normalized and linearly independent. And its corresponding MD-splines have local support, obey the convex hull and piecewise polynomial properties, and are C min { m , n } continuous, where m , n are different degrees of two adjoining segments. Compared with Sederberg et al. (2003), the MD-splines in this paper involve some of its cases and have higher order continuity in some cases.

Structural and Functional Studies of Truncated Hemolysin A from Proteus mirabilis

In this study we analyzed the structure and function of a truncated form of hemolysin A (HpmA265) from Proteus mirabilis using a series of functional and structural studies. Hemolysin A belongs to the two-partner secretion pathway. The two-partner secretion pathway has been identified as the most common protein secretion pathway among Gram-negative bacteria. Currently, the mechanism of action for the two-partner hemolysin members is not fully understood. In this study, hemolysis experiments revealed a unidirectional, cooperative, biphasic activity profile after full-length, inactive hemolysin A was seeded with truncated hemolysin A. We also solved the first x-ray structure of a TpsA hemolysin. The truncated hemolysin A formed a right-handed parallel beta-helix with three adjoining segments of anti-parallel beta-sheet. A CXXC disulfide bond, four buried solvent molecules, and a carboxyamide ladder were all located at the third complete beta-helix coil. Replacement of the CXXC motif led to decreased activity and stability according to hemolysis and CD studies. Furthermore, the crystal structure revealed a sterically compatible, dry dimeric interface formed via anti-parallel beta-sheet interactions between neighboring beta-helix monomers. Laser scanning confocal microscopy further supported the unidirectional interconversion of full-length hemolysin A. From these results, a model has been proposed, where cooperative, beta-strand interactions between HpmA265 and neighboring full-length hemolysin A molecules, facilitated in part by the highly conserved CXXC pattern, account for the template-assisted hemolysis.

Is Hepatectomy Beneficial in the Treatment of Multinodular Hepatocellular Carcinoma?

Background/Purpose Hepatectomy remains the standard treatment for primary hepatocellular carcinoma (HCC). However, its role in the treatment of multinodular HCC (MNHCC) is unknown. Methods The study consisted of 599 patients undergoing curative hepatic resection for HCC between October 1990 and June 2006, in which 112 patients had MNHCC (tumor number ≥ 2). The type of MNHCC was classified into: A, nodules involving one or two adjoining segments; B, large tumor with satellite nodules involving three or more segments; C, three or fewer nodules that are scattered in remote segments; and D, more than three separate tumors. Univariate and multivariate analyses were used to identify the prognostic factors related to postoperative survival. During the same period of time, and from our database of 178 patients with pathologically proven MNHCC who were undergoing nonsurgical multidisciplinary therapy, 48 patients with serum albumin level ≥ 3.5 g/dL, total bilirubin < 2 mg/dL, tumor number ≤ 3, and tumor size ≤ 5 cm were compared with 38 patients with the same condition treated with hepatectomy, in which 16 received one-block resection and 22 underwent multiple-site resection. Results The overall 1-, 3- and 5-year survival rates for patients with single-tumor HCC and MNHCC were 88.0%, 69.2% and 58.4%, and 86.1%, 55.5% and 29.9%, respectively ( p < 0.001). Alpha-fetoprotein > 400 ng/mL, total tumor size > 5 cm, largest tumor size > 5 cm, total tumor number > 3, microvascular invasion, non-A type MNHCC and multiple-site resection were poor prognostic factors for MNHCC in the hepatectomy group. Multivariate analysis revealed that only multiple-site hepatic resection was an independent adverse factor related to postoperative survival. In addition, patients who underwent one-block resection had significantly better survival compared with the nonsurgical group ( p = 0.0016), but the multiple-site resection subgroup did not. Conclusion The prognosis of MNHCC is poor in comparison with that of single-nodular HCC. Hepatectomy is the treatment of choice if the tumors can be removed by one-block resection and liver function reserve is acceptable.

Probing the Beta‐Amyloid Structure and Function of Hemolysin A

In this study we aimed to analyze the structure and function of a truncated form of hemolysin A from Proteus mirabilis using a combination of template‐assisted hemolysis and x‐ray crystallography. The hemolysis assay performed in the presence of both truncated and full‐length hemolysin A noted a cross‐seeded, biphasic activity profile, where the biphasic nature could be eliminated upon pre‐incubation of the protein components in the absence of red blood cells. X‐ray structure analysis of truncated hemolysin A reported a right‐handed parallel beta‐helix fold with three adjoining segments of anti‐parallel beta‐sheet, three buried solvent molecules near the disulfide bond between cysteines 144 and 147, and a unique dry dimeric interface. The disulfide bond stabilizes a unique beta‐arc between beta‐strands 11 and 12, which form two sides of the third full solenoid turn within right‐handed beta‐helix. The unusual dry dimeric interface propagates the monomeric beta‐helix structure forming a fibril appearance. The biochemical and structural results are discussed in reference to the propagation of beta‐amyloid type infectious prion diseases via a template‐assisted model.

Predicting the shapes of bones at a joint: application to the shoulder

This paper presents a novel method to explore the intrinsic morphological correlation between the bones of a shoulder joint (humerus and scapula). To model this correlation, canonical correlation analysis (CCA) is used. We also propose a technique to predict a three-dimensional (3D) bone shape from its adjoining segment at a joint based on partial least squares regression (PLS). The high dimensional 3D surface information of a bone is represented by a few variables using principal component analysis, which also captures the pattern of variability of the shapes in our datasets. Our results show that the humerus set and scapula set have highly linear morphological relationship and that the correlation information can be used as a classifier. In this study, primate shoulder bone datasets were categorised into two clusters: great apes (including humans) and monkeys. A leave one out experiment was performed to test the robustness of this prediction method. The prediction behaviour using this method shows statistically significantly better results than using the mean shape from the training set.

Zervikale Bandscheibenprothesen

Endoprosthetic replacement for spinal cord disorders represents an attractive alternative to fusion in those cases where surgery appears necessary for degenerative disc disease. At least in theory it has been proven that placement of an endoprosthesis minimizes undue stress on the adjoining segments and its possible negative consequences. Furthermore, cervical endoprostheses facilitate speedier rehabilitation and the problems involved in removal of the bone chip become irrelevant. Clinical results reported to date for the cervical spine are very encouraging and indicate that endoprosthetic replacement has been quite successful particularly for difficulties in multilevel approaches. However, long-term results for cervical endoprostheses have not yet been published and therefore at present there are no reference values for the viability of the prosthesis with regard to the aseptic loosening rate. There are also no findings available on how the implanted cervical prosthesis will behave when bone quality diminishes at an advanced age.

Asymptotic statistics of the n-sided planar Poisson–Voronoi cell: I. Exact results

We achieve a detailed understanding of then-sided planar Poisson–Voronoi cell in the limit of largen. Letpn be the probabilityfor a cell to have n sides. We construct the asymptotic expansion oflogpn up to terms that vanish as n → ∞. We obtain the statistics of the lengths of the perimeter segments and of the anglesbetween adjoining segments: to leading order as n → ∞, and after appropriate scaling, these become independentrandom variables whose laws we determine; and to next order in1/n they have nontrivial long range correlations whose expressions we provide. Then-sided cell tends towardsa circle of radius (n/4πλ)1/2, where λ is the cell density; hence Lewis’s law for the average areaAn ofthe n-sided cell behaves as An ≃ cn/λ with c = 1/4. For n → ∞ the cell perimeter, expressed as a functionR(ϕ) of thepolar angle ϕ, satisfies d2R/d ϕ2 = F(ϕ), where F is the known Gaussian noise; we deduce from it the probability law for the perimeter’s longwavelength deviations from circularity. Many other quantities related to the asymptotic cellshape become accessible to calculation.

Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes

BackgroundThe purpose of this work was to characterize the expression of drug and nutrient carriers along the anterior-posterior and crypt-villus axes of the intestinal epithelium and to study the validity of utilizing whole gut tissue rather than purified epithelial cells to examine regional variations in gene expression.ResultsWe have characterized the mRNA expression profiles of 76 % of all currently known transporters along the anterior-posterior axis of the gut. This is the first study to describe the expression profiles of the majority of all known transporters in the intestine. The expression profiles of transporters, as defined according to the Gene Ontology consortium, were measured in whole tissue of the murine duodenum, jejunum, ileum and colon using high-density microarrays. For nine transporters (Abca1, Abcc1, Abcc3, Abcg8, Slc10a2, Slc28a2, Slc2a1, Slc34a2 and Slc5a8), the mRNA profiles were further measured by RT-PCR in laser micro-dissected crypt and villus epithelial cells corresponding to the aforementioned intestinal regions. With respect to differentially regulated transporters, the colon had a distinct expression profile from small intestinal segments. The majority (59 % for p cutoff ≤ 0.05) of transporter mRNA levels were constant across the intestinal sections studied. For the transporter subclass "carrier activity", which contains the majority of known carriers for biologically active compounds, a significant change (p ≤ 0.05) along the anterior-posterior axis was observed.ConclusionAll nine transporters examined in laser-dissected material demonstrated good replication of the region-specific profiles revealed by microarray. Furthermore, we suggest that the distribution characteristics of Slc5a8 along the intestinal tract render it a suitable candidate carrier for monocarboxylate drugs in the posterior portion of the intestine. Our findings also predict that there is a significant difference in the absorption of carrier-mediated compounds in the different intestinal segments. The most pronounced differences can be expected between the adjoining segments ileum and colon, but the differences between the other adjoining segments are not negligible. Finally, for the examined genes, profiles measured in whole intestinal tissue extracts are representative of epithelial cell-only gene expression.

Tsunami history of an Oregon coastal lake reveals a 4600 yr record of great earthquakes on the Cascadia subduction zone

Bradley Lake, on the southern Oregon coastal plain, records local tsunamis and seismic shaking on the Cascadia subduction zone over the last 7000 yr. Thirteen marine incursions delivered landward-thinning sheets of sand to the lake from nearshore, beach, and dune environments to the west. Following each incursion, a slug of marine water near the bottom of the freshwater lake instigated a few-year-to-several-decade period of a brackish (≤4‰ salinity) lake. Four additional disturbances without marine incursions destabilized sideslopes and bottom sediment, producing a suspension deposit that blanketed the lake bottom. Considering the magnitude and duration of the disturbances necessary to produce Bradley Lake’s marine incursions, a local tsunami generated by a great earthquake on the Cascadia subduction zone is the only accountable mechanism. Extreme ocean levels must have been at least 5–8 m above sea level, and the cumulative duration of each marine incursion must have been at least 10 min. Disturbances without marine incursions require seismic shaking as well. Over the 4600 yr period when Bradley Lake was an optimum tsunami recorder, tsunamis from Cascadia plate-boundary earthquakes came in clusters. Between 4600 and 2800 cal yr B.P., tsunamis occurred at the average frequency of ~3–4 every 1000 yr. Then, starting ~2800 cal yr B.P., there was a 930–1260 yr interval with no tsunamis. That gap was followed by a ~1000 yr period with 4 tsunamis. In the last millennium, a 670–750 yr gap preceded the A.D. 1700 earthquake and tsunami. The A.D. 1700 earthquake may be the fi rst of a new cluster of plate-boundary earthquakes and accompanying tsunamis. Local tsunamis entered Bradley Lake an average of every 390 yr, whereas the portion of the Cascadia plate boundary that underlies Bradley Lake ruptured in a great earthquake less frequently, about once every 500 yr. Therefore, the entire length of the subduction zone does not rupture in every earthquake, and Bradley Lake has recorded earthquakes caused by rupture along the entire length of the Cascadia plate boundary as well as earthquakes caused by rupture of shorter segments of the boundary. The tsunami record from Bradley Lake indicates that at times, most recently ~1700 yr B.P., overlapping or adjoining segments of the Cascadia plate boundary ruptured within decades of each other.

Countering cooperative effects in protease inhibitors using constrained beta-strand-mimicking templates in focused combinatorial libraries.

A major problem in de novo design of enzyme inhibitors is the unpredictability of the induced fit, with the shape of both ligand and enzyme changing cooperatively and unpredictably in response to subtle structural changes within a ligand. We have investigated the possibility of dampening the induced fit by using a constrained template as a replacement for adjoining segments of a ligand. The template preorganizes the ligand structure, thereby organizing the local enzyme environment. To test this approach, we used templates consisting of constrained cyclic tripeptides, formed through side chain to main chain linkages, as structural mimics of the protease-bound extended beta-strand conformation of three adjoining amino acid residues at the N- or C-terminal sides of the scissile bond of substrates. The macrocyclic templates were derivatized to a range of 30 structurally diverse molecules via focused combinatorial variation of nonpeptidic appendages incorporating a hydroxyethylamine transition-state isostere. Most compounds in the library were potent inhibitors of the test protease (HIV-1 protease). Comparison of crystal structures for five protease-inhibitor complexes containing an N-terminal macrocycle and three protease-inhibitor complexes containing a C-terminal macrocycle establishes that the macrocycles fix their surrounding enzyme environment, thereby permitting independent variation of acyclic inhibitor components with only local disturbances to the protease. In this way, the location in the protease of various acyclic fragments on either side of the macrocyclic template can be accurately predicted. This type of templating strategy minimizes the problem of induced fit, reducing unpredictable cooperative effects in one inhibitor region caused by changes to adjacent enzyme-inhibitor interactions. This idea might be exploited in template-based approaches to inhibitors of other proteases, where a beta-strand mimetic is also required for recognition, and also other protein-binding ligands where different templates may be more appropriate.

Mortality Dependence of Cu Dual Damascene Interconnects on Adjacent Segment

AbstractThree terminal ‘dotted-I’ interconnect structures, with vias at both ends and an additional via in the middle, were tested under a variety of test conditions. Failures (mortalities) were observed even when segments were tested under conditions that would not have led to failure in two-terminal structures. Mortalities were found in right segments with jL values as low as 1250 A/cm, which is lower when compared to the immortality condition (jL)cr of 3700 A/cm reported for similar via-terminated structures. Moreover, we found that the mortality of a dotted-I segment is dependent on the direction and magnitude of the current in the adjacent segment. These results suggest that there is not a definite value of the jL product that defines true immortality in individual segments that are part of an interconnect tree. More importantly, the critical jL value for a single segment of Cu interconnects may be reduced or increased by an adjacent segment. Therefore independently determined (jL)cr values cannot be directly applied to interconnects with branched segments, but rather the magnitude as well as the direction of the current flow in the adjoining segments must be taken into consideration in evaluating the immortality of interconnect segments in an interconnect network.

Conformational similarities in the beta-ionone ring region of the rhodopsin chromophore in its ground state and after photoactivation to the metarhodopsin-I intermediate.

High-resolution solid-state NMR methods have been used to analyze the conformation of the chromophore in the late photointermediate metarhodopsin-I, from observation of (13)C nuclei introduced into the beta-ionone ring (at the C16, C17, and C18 methyl groups) and into the adjoining segment of the polyene chain (at C8). Bovine rhodopsin in its native membrane was also regenerated with retinal that was (13)C-labeled close to the 11-Z bond (C20 methyl group) to provide a reporter for optimizing and quantifying the photoconversion to metarhodopsin-I. Indirect photoconversion via the primary intermediate, bathorhodopin, was adopted as the preferred method since approximately 44% conversion to the metarhodopsin-I component could be achieved, with only low levels (approximately 18%) of ground-state rhodopsin remaining. The additional photoproduct, isorhodopsin, was resolved in (13)C spectra from C8 in the chain, at levels of approximately 38%, and was shown using rotational resonance NMR to adopt the 6-s-cis conformation between the ring and the polyene chain. The C8 resonance was not shifted in the metarhodopsin-I spectral component but was strongly broadened, revealing that the local conformation had become less well defined in this segment of the chain. This line broadening slowed rotational resonance exchange with the C17 and C18 ring methyl groups but was accounted for to show that, despite the chain being more relaxed in metarhodopsin-I, its average conformation with respect to the ring was similar to that in the ground state protein. Conformational restraints are also retained for the C16 and C17 methyl groups on photoactivation, which, together with the largely preserved conformation in the chain, argues convincingly that the ring remains with strong contacts in its binding pocket prior to activation of the receptor. Previous conclusions based on photocrosslinking studies are considered in view of the current findings.

Gymnastics

The purpose of the study was to quantify the muscle torques required in the performance of an optimised Yurchenko layout vault based on a five‐segment rigid link model and using input data from an elite female gymnast. At impact, the wrist torque trajectory indicated an extension‐flexion action while the shoulder was characterised by extension. The approximate 100 Nm (wrist flexor) and 125 Nm (shoulder extensor) respective peak torque magnitudes indicated that the impact action is not passive in nature. The contribution of joint torques to the adjoining segments was apportioned to the relative components namely; centripetal, gravity and net joint torque components. Despite the presence of both large wrist and shoulder joint torques, the net turning effect on the upper limb and hand segments about their centre of mass (CM) was small. The principal role of the upper limb joint torques was therefore to effect the appropriate joint motions and to support the weight of the gymnast. The performance of the optimum vault was primarily the result of the interplay between the centripetal and the net joint torque components at the wrist, hip and shoulder joints. This has implications to the performer in that successful execution of the vault is principally concerned with the ability to create a high angular momentum for horse impact and to then apply an appropriate level of joint torques that will make optimal use of the initial kinetic condition.